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Plasmacytoid dendritic cells sequester high prion titres at early stages of prion infection

Prions, which are rogue proteins that cause infectious and fatal degenerative disorders of the central nervous including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle and scrapie in sheep and goats, are not only found in the brain, but also in other tissues, particularly in lymphoid organs, long before they are detectable in the central nervous system.

Prions, which are rogue proteins that cause infectious and fatal degenerative disorders of the central nervous including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle and scrapie in sheep and goats, are not only found in the brain, but also in other tissues, particularly in lymphoid organs, long before they are detectable in the central nervous system. While a considerable body of evidence shows that B lymphocytes and follicular dendritic cells play a major role in this prion colonization of lymphoid organs, the contribution of various other cell types, including other antigen-presenting cells, to the accumulation and the spread of prions in the lymphoreticular system (LRS) are not well understood. It is therefore of great interest to better characterize how prions colonize the periphery after an infection and how they ultimately reach the brain, since such knowledge could help with treatment development. By taking advantage of a technique called magnetic cell isolation this study determined the infectious state of various immune cells, isolated from spleens of prion-infected mice. Through this they detected a high proportion of prions in cells of the innate immune system, particularly in plasmacytoid dendritic cells and natural killer cells. Two cell types that have previously not been associated with prion pathogenesis. Additionally, they also found that small amounts of prions are released from infected cells, a finding which raises the question of whether prions could spread in a similar manner to some viruses. Thus suggesting that prion-carrying immune cells that reside in the periphery may pose a major risk for dissemination if mobilized, for example, by an activation of the immune system.